Metformin Promotes the Protection of Mice Infected With Plasmodium yoelii Independently of γδ T Cell Expansion

Mana Miyakoda, Ganchimeg Bayarsaikhan, Daisuke Kimura, Masoud Akbari, Heiichiro Udono, Katsuyuki Yui

Research output: Contribution to journalArticle

Abstract

Adaptive immune responses are critical for protection against infection with Plasmodium parasites. The metabolic state dramatically changes in T cells during activation and the memory phase. Recent findings suggest that metformin, a medication for treating type-II diabetes, enhances T-cell immune responses by modulating lymphocyte metabolism. In this study, we investigated whether metformin could enhance anti-malaria immunity. Mice were infected with Plasmodium yoelii and administered metformin. Levels of parasitemia were reduced in treated mice compared with those in untreated mice, starting at ~2 weeks post-infection. The number of γδ T cells dramatically increased in the spleens of treated mice compared with that in untreated mice during the later phase of infection, while that of αβ T cells did not. The proportions of Vγ1+ and Vγ2+ γδ T cells increased, suggesting that activated cells were selectively expanded. However, these γδ T cells expressed inhibitory receptors and had severe defects in cytokine production, suggesting that they were in a state of exhaustion. Metformin was unable to rescue the cells from exhaustion at this stage. Depletion of γδ T cells with antibody treatment did not affect the reduction of parasitemia in metformin-treated mice, suggesting that the effect of metformin on the reduction of parasitemia was independent of γδ T cells.

Original languageEnglish
Number of pages1
JournalFrontiers in Immunology
Volume9
DOIs
Publication statusPublished - Jan 1 2018

Fingerprint

Plasmodium yoelii
Metformin
T-Lymphocytes
Parasitemia
Malaria
Costimulatory and Inhibitory T-Cell Receptors
Adaptive Immunity
Infection
Type 2 Diabetes Mellitus
Immunity
Parasites
Spleen
Lymphocytes
Cytokines
Antibodies

Keywords

  • clonal expansion
  • malaria
  • metabolism
  • metformin
  • protection
  • γδ T cell

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Metformin Promotes the Protection of Mice Infected With Plasmodium yoelii Independently of γδ T Cell Expansion. / Miyakoda, Mana; Bayarsaikhan, Ganchimeg; Kimura, Daisuke; Akbari, Masoud; Udono, Heiichiro; Yui, Katsuyuki.

In: Frontiers in Immunology, Vol. 9, 01.01.2018.

Research output: Contribution to journalArticle

Miyakoda, Mana ; Bayarsaikhan, Ganchimeg ; Kimura, Daisuke ; Akbari, Masoud ; Udono, Heiichiro ; Yui, Katsuyuki. / Metformin Promotes the Protection of Mice Infected With Plasmodium yoelii Independently of γδ T Cell Expansion. In: Frontiers in Immunology. 2018 ; Vol. 9.
@article{c4c1f7548abd4323bb4b0c39ca8dc10a,
title = "Metformin Promotes the Protection of Mice Infected With Plasmodium yoelii Independently of γδ T Cell Expansion",
abstract = "Adaptive immune responses are critical for protection against infection with Plasmodium parasites. The metabolic state dramatically changes in T cells during activation and the memory phase. Recent findings suggest that metformin, a medication for treating type-II diabetes, enhances T-cell immune responses by modulating lymphocyte metabolism. In this study, we investigated whether metformin could enhance anti-malaria immunity. Mice were infected with Plasmodium yoelii and administered metformin. Levels of parasitemia were reduced in treated mice compared with those in untreated mice, starting at ~2 weeks post-infection. The number of γδ T cells dramatically increased in the spleens of treated mice compared with that in untreated mice during the later phase of infection, while that of αβ T cells did not. The proportions of Vγ1+ and Vγ2+ γδ T cells increased, suggesting that activated cells were selectively expanded. However, these γδ T cells expressed inhibitory receptors and had severe defects in cytokine production, suggesting that they were in a state of exhaustion. Metformin was unable to rescue the cells from exhaustion at this stage. Depletion of γδ T cells with antibody treatment did not affect the reduction of parasitemia in metformin-treated mice, suggesting that the effect of metformin on the reduction of parasitemia was independent of γδ T cells.",
keywords = "clonal expansion, malaria, metabolism, metformin, protection, γδ T cell",
author = "Mana Miyakoda and Ganchimeg Bayarsaikhan and Daisuke Kimura and Masoud Akbari and Heiichiro Udono and Katsuyuki Yui",
year = "2018",
month = "1",
day = "1",
doi = "10.3389/fimmu.2018.02942",
language = "English",
volume = "9",
journal = "Frontiers in Immunology",
issn = "1664-3224",
publisher = "Frontiers Media S. A.",

}

TY - JOUR

T1 - Metformin Promotes the Protection of Mice Infected With Plasmodium yoelii Independently of γδ T Cell Expansion

AU - Miyakoda, Mana

AU - Bayarsaikhan, Ganchimeg

AU - Kimura, Daisuke

AU - Akbari, Masoud

AU - Udono, Heiichiro

AU - Yui, Katsuyuki

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Adaptive immune responses are critical for protection against infection with Plasmodium parasites. The metabolic state dramatically changes in T cells during activation and the memory phase. Recent findings suggest that metformin, a medication for treating type-II diabetes, enhances T-cell immune responses by modulating lymphocyte metabolism. In this study, we investigated whether metformin could enhance anti-malaria immunity. Mice were infected with Plasmodium yoelii and administered metformin. Levels of parasitemia were reduced in treated mice compared with those in untreated mice, starting at ~2 weeks post-infection. The number of γδ T cells dramatically increased in the spleens of treated mice compared with that in untreated mice during the later phase of infection, while that of αβ T cells did not. The proportions of Vγ1+ and Vγ2+ γδ T cells increased, suggesting that activated cells were selectively expanded. However, these γδ T cells expressed inhibitory receptors and had severe defects in cytokine production, suggesting that they were in a state of exhaustion. Metformin was unable to rescue the cells from exhaustion at this stage. Depletion of γδ T cells with antibody treatment did not affect the reduction of parasitemia in metformin-treated mice, suggesting that the effect of metformin on the reduction of parasitemia was independent of γδ T cells.

AB - Adaptive immune responses are critical for protection against infection with Plasmodium parasites. The metabolic state dramatically changes in T cells during activation and the memory phase. Recent findings suggest that metformin, a medication for treating type-II diabetes, enhances T-cell immune responses by modulating lymphocyte metabolism. In this study, we investigated whether metformin could enhance anti-malaria immunity. Mice were infected with Plasmodium yoelii and administered metformin. Levels of parasitemia were reduced in treated mice compared with those in untreated mice, starting at ~2 weeks post-infection. The number of γδ T cells dramatically increased in the spleens of treated mice compared with that in untreated mice during the later phase of infection, while that of αβ T cells did not. The proportions of Vγ1+ and Vγ2+ γδ T cells increased, suggesting that activated cells were selectively expanded. However, these γδ T cells expressed inhibitory receptors and had severe defects in cytokine production, suggesting that they were in a state of exhaustion. Metformin was unable to rescue the cells from exhaustion at this stage. Depletion of γδ T cells with antibody treatment did not affect the reduction of parasitemia in metformin-treated mice, suggesting that the effect of metformin on the reduction of parasitemia was independent of γδ T cells.

KW - clonal expansion

KW - malaria

KW - metabolism

KW - metformin

KW - protection

KW - γδ T cell

UR - http://www.scopus.com/inward/record.url?scp=85059926386&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85059926386&partnerID=8YFLogxK

U2 - 10.3389/fimmu.2018.02942

DO - 10.3389/fimmu.2018.02942

M3 - Article

VL - 9

JO - Frontiers in Immunology

JF - Frontiers in Immunology

SN - 1664-3224

ER -